title: Mammalian cardiac regeneration after fetal myocardial infarction requires cardiac progenitor cell recruitment.
abstract: BACKGROUND
  In contrast to the adult, fetal sheep consistently regenerate functional myocardium after myocardial infarction. We hypothesize that this regeneration is due to the recruitment of cardiac progenitor cells to the infarct by stromal-derived factor-1α (SDF-1α) and that its competitive inhibition will block the regenerative fetal response.
  
  
  METHODS
  A 20% apical infarct was created in adult and fetal sheep by selective permanent coronary artery ligation. Lentiviral overexpression of mutant SDF-1α competitively inhibited SDF-1α in fetal infarcts. Echocardiography was performed to assess left ventricular function and infarct size. Cardiac progenitor cell recruitment and proliferation was assessed in fetal infarcts at 1 month by immunohistochemistry for nkx2.5 and 5-bromo-2-deoxyuridine.
  
  
  RESULTS
  Competitive inhibition of SDF-1α converted the regenerative fetal response into a reparative response, similar to the adult. SDF-inhibited fetal infarcts demonstrated significant infarct expansion by echocardiography (p < 0.001) and a significant decrease in the number of nkx2.5+ cells repopulating the infarct (p < 0.001).
  
  
  CONCLUSIONS
  The fetal regenerative response to myocardial infarction requires the recruitment of cardiac progenitor cells and is dependent on SDF1α. This novel model of mammalian cardiac regeneration after myocardial infarction provides a powerful tool to better understand cardiac progenitor cell biology and to develop strategies to cardiac regeneration in the adult.
authors.affiliation: Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104-5156, USA.
authors.forename: Myron
authors.initials: M
authors.lastname: Allukian
authors.forename: Junwang
authors.initials: J
authors.lastname: Xu
authors.forename: Michael
authors.initials: M
authors.lastname: Morris
authors.forename: Robert
authors.initials: R
authors.lastname: Caskey
authors.forename: Wanda
authors.initials: W
authors.lastname: Dorsett-Martin
authors.forename: Theodore
authors.initials: T
authors.lastname: Plappert
authors.forename: Michael
authors.initials: M
authors.lastname: Griswold
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Gorman
authors.forename: Robert C
authors.initials: RC
authors.lastname: Gorman
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Liechty
mesh_terms: D000818:Animals; D054377:Chemokine CXCL12 / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005315:Fetal Diseases / Q000473:pathology*; D006321:Heart / Q000502:physiology*; D009203:Myocardial Infarction / Q000196:embryology* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000502:physiology; D011247:Pregnancy; D011270:Pregnancy, Animal; D012038:Regeneration / Q000502:physiology*; D012756:Sheep; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*
chemical_list: D054377:Chemokine CXCL12